COX inhibitors

Aspirin

Clopidogrel

Adenosine diphosphate (ADP) receptor inhibitors

Examples include:

• Clopidogrel
• Prasugrel
• Ticagrelor
• Ticlopidine

Mechanism of ADP receptor inhibitors

• Adenosine diphosphate (ADP) is one of the main platelet activation factors, mediated by G-coupled receptors P2Y1 and P2Y12.
• The main target of ADP receptor inhibition is the P2Y12 receptor, as it is the one which leads to sustained platelet aggregation and stabilisation of the platelet plaque.

Ticagrelor REVERSIBLY inhibits the binding of ADP and directly blocks its platelet P2Y12-receptors, which are important in the activation of platelets → inhibiting platelet activation and aggregation.

The thienopyridines (clopidogrel and prasugrel) act as a prodrug, one of whose metabolites IRREVERSIBLY inhibits the binding of ADP to its platelet P2Y12 receptor. Therefore ADP is unable to activate the glycoprotein GPIIb/IIIa complex which inhibits platelet aggregation.

Evidence

• As aspirin and ADP inhibitors work by blocking different platelet aggregation pathways, their potential synergy has been studied by multiple clinical trials, particularly in high-risk patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).
• Clopidogrel used to be the most commonly used ADP inhibitor, however, due to its interindividual variability in antiplatelet effects, newer agents such as prasugrel and ticagrelor have been developed.